This proposal represents a collaboration between the University of Zimbabwe-UCSF Women's Health Programme in Harare, Zimbabwe (led by Dr. Nancy Padian at UCSF), and the Zimbabwe AIDS Prevention Program (ZAPP, led by Dr. Yvonne Maldinado), and the HIV/AIDS Research Group at the San Francisco Departrnent of Public Health (led by Dr. Susan Buchbinder). Dr. Tsungai Chipato from the University of Zimbabwe will be Principal Investigator for the overall program. Together, we bring to the new HPTN two strong research sites (one international [consisting of both the UZ-UCSF Program and ZAPP] and one domestic) and substantial expertise in epidemiology, clinical trials design, clinical medicine, behavioral science, biostatistics, virology and data management. We have strong ties with HIV-infected and at-risk populations in Zimbabwe and San Francisco, and can ensure active community involvement in the planning and implementation of trials. Even more than the fruitful collaboration between separate HPTN sites, a combined site will foster synergy and communication between investigators representing a wide range of expertise. It will be cost effective by funding investigators and staff at the combined site to work on multiple projects. The science arising from such combined sites also benefit from the broad focus brought to prevention research by the need to integrate domestic and international concerns, and develop prevention strategies for different modes of sexual transmission. Integration of the two community advisory boards will deepen understanding, disseminate complementary skills, and ultimately enhance the contribution of affected communities to the research agenda. In this proposal, we will continue four existing HIVNET studies: HIVNET 016, an international Phase III clinical trial of the microbicidal effects of N-9 gel on STDs and HIV; HIVNET 021, an international observational study to determine the effect of hormonal contraception on the acquisition of STDs and HIV; HIVNET 015, a domestic Phase III behavioral trial comparing an intensive individualized behavioral intervention with standard counseling and testing among high-risk MSM; and HIVNET 023, an international safety and dosing study of nevirapine for post-natal prevention of HIV transmission. In addition, we also propose new domestic Phase I trials both for antiretroviral therapy (ART) and rectal and vaginal microbicides. Thus we propose four specific aims: l) To provide scientific expertise and leadership to the network specifically in the areas of: a) rectal and vaginal microbicide and barrier contraceptive research; b) identification and implementation of interventions to reduce high-risk sexual behavior; c) use of anti-retroviral therapy to prevent transmission; d) research on prevention of perinatal transmission; 2) to conduct and participate in Phase I, II and/or III prevention intervention clinical trials domestically and internationally; 3) to convene and maintain community advisory boards in San Francisco and in Zimbabwe and to link them; 4) to demonstrate our ability to expand to multiple prevention efficacy trials in new populations.